UA57071C2 - ПОХІДНІ 5-АРИЛ-3-(8-АЗАБІЦИКЛО[3.2.1]ОКТ-3-ІЛ)-1,3,4-ОКСАДІАЗОЛ-2(3Н)-ОНУ ЯК ЛІГАНДИ РЕЦЕПТОРА 5-HT4, СПОСІБ ЇХ ОДЕРЖАННЯ, ФАРМАЦЕВТИЧНА КОМПОЗИЦІЯ ТА ЛІКАРСЬКИЙ ЗАСІБ НА ЇХ ОСНОВІ - Google Patents

ПОХІДНІ 5-АРИЛ-3-(8-АЗАБІЦИКЛО[3.2.1]ОКТ-3-ІЛ)-1,3,4-ОКСАДІАЗОЛ-2(3Н)-ОНУ ЯК ЛІГАНДИ РЕЦЕПТОРА 5-HT4, СПОСІБ ЇХ ОДЕРЖАННЯ, ФАРМАЦЕВТИЧНА КОМПОЗИЦІЯ ТА ЛІКАРСЬКИЙ ЗАСІБ НА ЇХ ОСНОВІ Download PDF

Info

Publication number: UA57071C2
Authority: UA; Ukraine
Prior art keywords: general formula; group; compound; chloro; mixture
Prior art date: 1997-04-18

Application number

UA99105665A

Other languages

English (en)

Russian (ru)

Ukrainian (uk)

Inventor

Самір Жегам

Алістер Локхед

Фредерік Галлі

Фредерик Галли

Ален Неделек

Аксель САМСОН

Т'єррі Галле

Original Assignee

Санофі-Сентелябо

Санофи-Сентелябо

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1997-04-18

Filing date

1998-04-15

Publication date

2003-06-16

1998-04-15 Application filed by Санофі-Сентелябо, Санофи-Сентелябо filed Critical Санофі-Сентелябо

2003-06-16 Publication of UA57071C2 publication Critical patent/UA57071C2/uk

Links

239000003446 ligand Substances 0.000 title description 4
108091005482 5-HT4 receptors Proteins 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 69
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 13
125000000217 alkyl group Chemical group 0.000 claims abstract description 12
125000005843 halogen group Chemical group 0.000 claims abstract description 7
239000001257 hydrogen Substances 0.000 claims abstract description 6
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 6
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 5
125000004981 cycloalkylmethyl group Chemical group 0.000 claims abstract description 3
239000000203 mixture Substances 0.000 claims description 43
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 14
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 14
-1 4-(dimethylamino)-1-piperidyl Chemical group 0.000 claims description 10
238000000034 method Methods 0.000 claims description 9
239000002253 acid Substances 0.000 claims description 5
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
150000003839 salts Chemical class 0.000 claims description 5
YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 claims description 4
WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 claims description 4
NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 claims description 3
150000002148 esters Chemical class 0.000 claims description 3
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 claims description 3
125000006239 protecting group Chemical group 0.000 claims description 3
XLRPYZSEQKXZAA-OCAPTIKFSA-N tropane Chemical group C1CC[C@H]2CC[C@@H]1N2C XLRPYZSEQKXZAA-OCAPTIKFSA-N 0.000 claims description 3
125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 2
QIZDQFOVGFDBKW-DHBOJHSNSA-N Pseudotropine Natural products OC1C[C@@H]2[N+](C)[C@H](C1)CC2 QIZDQFOVGFDBKW-DHBOJHSNSA-N 0.000 claims description 2
125000003277 amino group Chemical group 0.000 claims description 2
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
229910052757 nitrogen Inorganic materials 0.000 claims description 2
125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
230000003287 optical effect Effects 0.000 claims description 2
239000000546 pharmaceutical excipient Substances 0.000 claims description 2
CYHOMWAPJJPNMW-JIGDXULJSA-N tropine Chemical compound C1[C@@H](O)C[C@H]2CC[C@@H]1N2C CYHOMWAPJJPNMW-JIGDXULJSA-N 0.000 claims description 2
230000003993 interaction Effects 0.000 claims 2
FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Chemical compound CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 claims 1
239000012458 free base Substances 0.000 claims 1
229940126601 medicinal product Drugs 0.000 claims 1
SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 claims 1
239000008194 pharmaceutical composition Substances 0.000 claims 1
AHWALFGBDFAJAI-UHFFFAOYSA-N phenyl carbonochloridate Chemical compound ClC(=O)OC1=CC=CC=C1 AHWALFGBDFAJAI-UHFFFAOYSA-N 0.000 claims 1
238000012876 topography Methods 0.000 claims 1
238000002560 therapeutic procedure Methods 0.000 abstract description 2
125000003545 alkoxy group Chemical group 0.000 abstract 1
125000003884 phenylalkyl group Chemical group 0.000 abstract 1
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 48
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 27
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 23
239000002904 solvent Substances 0.000 description 22
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 19
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 14
KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 12
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 12
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 11
208000035475 disorder Diseases 0.000 description 11
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
NMRPBPVERJPACX-UHFFFAOYSA-N octan-3-ol Chemical compound CCCCCC(O)CC NMRPBPVERJPACX-UHFFFAOYSA-N 0.000 description 8
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
238000012360 testing method Methods 0.000 description 8
239000002244 precipitate Substances 0.000 description 7
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
QTSFCTIYSBOIBJ-UHFFFAOYSA-N ethoxycarbonyliminocarbamic acid Chemical compound CCOC(=O)N=NC(O)=O QTSFCTIYSBOIBJ-UHFFFAOYSA-N 0.000 description 6
QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 6
239000000725 suspension Substances 0.000 description 6
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 5
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 5
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 5
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 5
238000001035 drying Methods 0.000 description 5
238000001914 filtration Methods 0.000 description 5
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 5
229910000041 hydrogen chloride Inorganic materials 0.000 description 5
239000012265 solid product Substances 0.000 description 5
230000009870 specific binding Effects 0.000 description 5
210000001519 tissue Anatomy 0.000 description 5
208000019901 Anxiety disease Diseases 0.000 description 4
241000700159 Rattus Species 0.000 description 4
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
239000008346 aqueous phase Substances 0.000 description 4
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 4
238000005119 centrifugation Methods 0.000 description 4
229940079593 drug Drugs 0.000 description 4
239000003814 drug Substances 0.000 description 4
239000012074 organic phase Substances 0.000 description 4
229910000027 potassium carbonate Inorganic materials 0.000 description 4
229940076279 serotonin Drugs 0.000 description 4
239000000741 silica gel Substances 0.000 description 4
229910002027 silica gel Inorganic materials 0.000 description 4
108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 3
102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 3
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
102000004384 Histamine H3 receptors Human genes 0.000 description 3
108090000981 Histamine H3 receptors Proteins 0.000 description 3
239000000010 aprotic solvent Substances 0.000 description 3
AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 3
210000004556 brain Anatomy 0.000 description 3
238000004587 chromatography analysis Methods 0.000 description 3
210000003238 esophagus Anatomy 0.000 description 3
229940095102 methyl benzoate Drugs 0.000 description 3
208000020016 psychiatric disease Diseases 0.000 description 3
108020003175 receptors Proteins 0.000 description 3
102000005962 receptors Human genes 0.000 description 3
239000013049 sediment Substances 0.000 description 3
239000007787 solid Substances 0.000 description 3
229950001870 spizofurone Drugs 0.000 description 3
238000005303 weighing Methods 0.000 description 3
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
MPPPKRYCTPRNTB-UHFFFAOYSA-N 1-bromobutane Chemical compound CCCCBr MPPPKRYCTPRNTB-UHFFFAOYSA-N 0.000 description 2
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
208000024827 Alzheimer disease Diseases 0.000 description 2
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
206010012289 Dementia Diseases 0.000 description 2
208000020401 Depressive disease Diseases 0.000 description 2
206010026749 Mania Diseases 0.000 description 2
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
229920002873 Polyethylenimine Polymers 0.000 description 2
208000028017 Psychotic disease Diseases 0.000 description 2
239000012300 argon atmosphere Substances 0.000 description 2
230000003542 behavioural effect Effects 0.000 description 2
AIXAANGOTKPUOY-UHFFFAOYSA-N carbachol Chemical compound [Cl-].C[N+](C)(C)CCOC(N)=O AIXAANGOTKPUOY-UHFFFAOYSA-N 0.000 description 2
229960004484 carbachol Drugs 0.000 description 2
210000000748 cardiovascular system Anatomy 0.000 description 2
230000001186 cumulative effect Effects 0.000 description 2
230000003001 depressive effect Effects 0.000 description 2
230000000694 effects Effects 0.000 description 2
238000002474 experimental method Methods 0.000 description 2
238000011534 incubation Methods 0.000 description 2
230000005764 inhibitory process Effects 0.000 description 2
239000007788 liquid Substances 0.000 description 2
210000004379 membrane Anatomy 0.000 description 2
239000012528 membrane Substances 0.000 description 2
210000001577 neostriatum Anatomy 0.000 description 2
230000009871 nonspecific binding Effects 0.000 description 2
239000000047 product Substances 0.000 description 2
238000010992 reflux Methods 0.000 description 2
238000010898 silica gel chromatography Methods 0.000 description 2
230000002485 urinary effect Effects 0.000 description 2
QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
FXHWYZDTCYFFCV-UHFFFAOYSA-N 4-amino-5-chloro-2-methoxybenzohydrazide Chemical compound COC1=CC(N)=C(Cl)C=C1C(=O)NN FXHWYZDTCYFFCV-UHFFFAOYSA-N 0.000 description 1
RVEATKYEARPWRE-UHFFFAOYSA-N 4-amino-5-chloro-2-methoxybenzoic acid Chemical compound COC1=CC(N)=C(Cl)C=C1C(O)=O RVEATKYEARPWRE-UHFFFAOYSA-N 0.000 description 1
206010003805 Autism Diseases 0.000 description 1
208000020706 Autistic disease Diseases 0.000 description 1
FVICGBKHOSCMMC-UHFFFAOYSA-N Br.O1C(NN=C1)=O Chemical compound Br.O1C(NN=C1)=O FVICGBKHOSCMMC-UHFFFAOYSA-N 0.000 description 1
208000032841 Bulimia Diseases 0.000 description 1
206010006550 Bulimia nervosa Diseases 0.000 description 1
206010007270 Carcinoid syndrome Diseases 0.000 description 1
241000700198 Cavia Species 0.000 description 1
241000700199 Cavia porcellus Species 0.000 description 1
206010008631 Cholera Diseases 0.000 description 1
206010012735 Diarrhoea Diseases 0.000 description 1
208000030814 Eating disease Diseases 0.000 description 1
208000019454 Feeding and Eating disease Diseases 0.000 description 1
208000010412 Glaucoma Diseases 0.000 description 1
206010020772 Hypertension Diseases 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
208000019695 Migraine disease Diseases 0.000 description 1
QKDDJDBFONZGBW-UHFFFAOYSA-N N-Cyclohexy-4-(imidazol-4-yl)-1-piperidinecarbothioamide Chemical compound C1CC(C=2NC=NC=2)CCN1C(=S)NC1CCCCC1 QKDDJDBFONZGBW-UHFFFAOYSA-N 0.000 description 1
206010028813 Nausea Diseases 0.000 description 1
208000012902 Nervous system disease Diseases 0.000 description 1
208000025966 Neurological disease Diseases 0.000 description 1
206010033864 Paranoia Diseases 0.000 description 1
208000027099 Paranoid disease Diseases 0.000 description 1
208000018737 Parkinson disease Diseases 0.000 description 1
208000008469 Peptic Ulcer Diseases 0.000 description 1
206010038563 Reocclusion Diseases 0.000 description 1
206010039966 Senile dementia Diseases 0.000 description 1
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
206010041349 Somnolence Diseases 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
208000007814 Unstable Angina Diseases 0.000 description 1
206010046543 Urinary incontinence Diseases 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
239000013543 active substance Substances 0.000 description 1
239000000556 agonist Substances 0.000 description 1
230000001270 agonistic effect Effects 0.000 description 1
238000002399 angioplasty Methods 0.000 description 1
230000003042 antagnostic effect Effects 0.000 description 1
239000005557 antagonist Substances 0.000 description 1
239000003146 anticoagulant agent Substances 0.000 description 1
239000003420 antiserotonin agent Substances 0.000 description 1
230000036506 anxiety Effects 0.000 description 1
230000004596 appetite loss Effects 0.000 description 1
229910052786 argon Inorganic materials 0.000 description 1
206010003119 arrhythmia Diseases 0.000 description 1
208000006673 asthma Diseases 0.000 description 1
229940054066 benzamide antipsychotics Drugs 0.000 description 1
150000003936 benzamides Chemical class 0.000 description 1
235000019445 benzyl alcohol Nutrition 0.000 description 1
238000009835 boiling Methods 0.000 description 1
125000004432 carbon atom Chemical group C* 0.000 description 1
UBAZGMLMVVQSCD-UHFFFAOYSA-N carbon dioxide;molecular oxygen Chemical compound O=O.O=C=O UBAZGMLMVVQSCD-UHFFFAOYSA-N 0.000 description 1
238000007675 cardiac surgery Methods 0.000 description 1
101150059448 cdk7 gene Proteins 0.000 description 1
210000003169 central nervous system Anatomy 0.000 description 1
208000026106 cerebrovascular disease Diseases 0.000 description 1
FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
230000001143 conditioned effect Effects 0.000 description 1
230000008602 contraction Effects 0.000 description 1
230000006735 deficit Effects 0.000 description 1
238000010586 diagram Methods 0.000 description 1
125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 1
125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
235000014632 disordered eating Nutrition 0.000 description 1
230000035622 drinking Effects 0.000 description 1
201000006549 dyspepsia Diseases 0.000 description 1
206010013990 dysuria Diseases 0.000 description 1
206010015037 epilepsy Diseases 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical group C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 description 1
239000003527 fibrinolytic agent Substances 0.000 description 1
230000003480 fibrinolytic effect Effects 0.000 description 1
206010016766 flatulence Diseases 0.000 description 1
239000012634 fragment Substances 0.000 description 1
230000002496 gastric effect Effects 0.000 description 1
208000021302 gastroesophageal reflux disease Diseases 0.000 description 1
210000005095 gastrointestinal system Anatomy 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
230000000742 histaminergic effect Effects 0.000 description 1
238000002329 infrared spectrum Methods 0.000 description 1
210000002011 intestinal secretion Anatomy 0.000 description 1
210000000936 intestine Anatomy 0.000 description 1
208000002551 irritable bowel syndrome Diseases 0.000 description 1
208000028867 ischemia Diseases 0.000 description 1
235000021266 loss of appetite Nutrition 0.000 description 1
208000019017 loss of appetite Diseases 0.000 description 1
230000014759 maintenance of location Effects 0.000 description 1
230000008018 melting Effects 0.000 description 1
238000002844 melting Methods 0.000 description 1
ALYQFGBPEGLBLW-UHFFFAOYSA-N methyl 4-amino-5-chloro-2-methoxybenzoate Chemical compound COC(=O)C1=CC(Cl)=C(N)C=C1OC ALYQFGBPEGLBLW-UHFFFAOYSA-N 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
238000004452 microanalysis Methods 0.000 description 1
210000004400 mucous membrane Anatomy 0.000 description 1
210000003205 muscle Anatomy 0.000 description 1
230000003387 muscular Effects 0.000 description 1
208000010125 myocardial infarction Diseases 0.000 description 1
230000008693 nausea Effects 0.000 description 1
230000000926 neurological effect Effects 0.000 description 1
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
210000000056 organ Anatomy 0.000 description 1
238000006213 oxygenation reaction Methods 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
230000007170 pathology Effects 0.000 description 1
239000012071 phase Substances 0.000 description 1
BSCCSDNZEIHXOK-UHFFFAOYSA-N phenyl carbamate Chemical compound NC(=O)OC1=CC=CC=C1 BSCCSDNZEIHXOK-UHFFFAOYSA-N 0.000 description 1
230000000704 physical effect Effects 0.000 description 1
UERQMZVFUXRQOD-UHFFFAOYSA-N piperidine-1-carbothioamide Chemical compound NC(=S)N1CCCCC1 UERQMZVFUXRQOD-UHFFFAOYSA-N 0.000 description 1
ZLMJMSJWJFRBEC-OUBTZVSYSA-N potassium-40 Chemical compound [40K] ZLMJMSJWJFRBEC-OUBTZVSYSA-N 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
238000002360 preparation method Methods 0.000 description 1
230000002265 prevention Effects 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
239000003586 protic polar solvent Substances 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
230000029058 respiratory gaseous exchange Effects 0.000 description 1
206010039083 rhinitis Diseases 0.000 description 1
208000012672 seasonal affective disease Diseases 0.000 description 1
230000000862 serotonergic effect Effects 0.000 description 1
239000000952 serotonin receptor agonist Substances 0.000 description 1
208000019116 sleep disease Diseases 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
230000006641 stabilisation Effects 0.000 description 1
238000011105 stabilization Methods 0.000 description 1
210000002784 stomach Anatomy 0.000 description 1
239000000126 substance Substances 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
230000002537 thrombolytic effect Effects 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
238000001665 trituration Methods 0.000 description 1
235000012431 wafers Nutrition 0.000 description 1
238000005406 washing Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
- C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system

Landscapes

Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Engineering & Computer Science (AREA)
Public Health (AREA)
Bioinformatics & Cheminformatics (AREA)
Urology & Nephrology (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Diabetes (AREA)
Hematology (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

UA99105665A 1997-04-18 1998-04-15 ПОХІДНІ 5-АРИЛ-3-(8-АЗАБІЦИКЛО[3.2.1]ОКТ-3-ІЛ)-1,3,4-ОКСАДІАЗОЛ-2(3Н)-ОНУ ЯК ЛІГАНДИ РЕЦЕПТОРА 5-HT4, СПОСІБ ЇХ ОДЕРЖАННЯ, ФАРМАЦЕВТИЧНА КОМПОЗИЦІЯ ТА ЛІКАРСЬКИЙ ЗАСІБ НА ЇХ ОСНОВІ UA57071C2 (uk)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
FR9704802A FR2762316B1 (fr)	1997-04-18	1997-04-18	Derives de 5-aryl-3-(8-azabicyclo[3.2.1] octan-3-yl)-1,3,4- oxadiazol-2(3h)-one, leur preparation et leur application en therapeutique
PCT/FR1998/000754 WO1998047898A1 (fr)	1997-04-18	1998-04-15	Derives de 5-aryl-3-(8-azabicyclo(3.2.2)oct-3-yl)-1,3,4-oxadiazol-2(3h)-one en tant que ligands des recepteurs 5-ht4

Publications (1)

Publication Number	Publication Date
UA57071C2 true UA57071C2 (uk)	2003-06-16

Family

ID=9506076

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
UA99105665A UA57071C2 (uk)	1997-04-18	1998-04-15	ПОХІДНІ 5-АРИЛ-3-(8-АЗАБІЦИКЛО[3.2.1]ОКТ-3-ІЛ)-1,3,4-ОКСАДІАЗОЛ-2(3Н)-ОНУ ЯК ЛІГАНДИ РЕЦЕПТОРА 5-HT<sub>4</sub>, СПОСІБ ЇХ ОДЕРЖАННЯ, ФАРМАЦЕВТИЧНА КОМПОЗИЦІЯ ТА ЛІКАРСЬКИЙ ЗАСІБ НА ЇХ ОСНОВІ

Country Status (32)

Country	Link
US (1)	US6255319B1 (de)
EP (1)	EP0975631B1 (de)
JP (1)	JP2001521542A (de)
KR (1)	KR20010006452A (de)
CN (1)	CN1260794A (de)
AR (1)	AR012458A1 (de)
AT (1)	ATE206424T1 (de)
AU (1)	AU742666B2 (de)
BG (1)	BG64053B1 (de)
BR (1)	BR9808926A (de)
CA (1)	CA2286106A1 (de)
CO (1)	CO4750656A1 (de)
CZ (1)	CZ289154B6 (de)
DE (1)	DE69801905T2 (de)
DK (1)	DK0975631T3 (de)
EE (1)	EE03769B1 (de)
ES (1)	ES2165162T3 (de)
FR (1)	FR2762316B1 (de)
HU (1)	HUP0002456A3 (de)
IL (1)	IL132352A0 (de)
NO (1)	NO995040L (de)
NZ (1)	NZ500396A (de)
PL (1)	PL186894B1 (de)
PT (1)	PT975631E (de)
RU (1)	RU2186066C2 (de)
SI (1)	SI0975631T1 (de)
SK (1)	SK283441B6 (de)
TR (1)	TR199902600T2 (de)
TW (1)	TW502005B (de)
UA (1)	UA57071C2 (de)
WO (1)	WO1998047898A1 (de)
ZA (1)	ZA983257B (de)

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB0211230D0 (en) *	2002-05-16	2002-06-26	Medinnova Sf	Treatment of heart failure
EP1610789B1 (de) *	2003-03-26	2010-07-21	Merck Sharp & Dohme Corp.	Bicyclische piperidin-derivate als melanocortin-4 rezeptor-agonisten
US7321042B2 (en) *	2003-10-16	2008-01-22	Boehringer Ingelheim Pharma Gmbh & Co. Kg	Process for preparing N-substituted 3-β-aminonortropanes
EP1686965A2 (de) *	2003-11-18	2006-08-09	Boehringer Ingelheim International GmbH	Feste pharmazeutische zubereitungsform
BRPI0512046A (pt)	2004-06-15	2008-02-06	Pfizer	derivados de ácido benzimidazolona carboxìlico
US7737163B2 (en)	2004-06-15	2010-06-15	Pfizer Inc.	Benzimidazolone carboxylic acid derivatives
FR2873693B1 (fr) *	2004-07-29	2006-09-15	Sanofi Synthelabo	Derives d'amino-tropane, leur preparation et leur application en therapeutique
CA2588037A1 (en) *	2004-12-22	2006-06-29	Theravance, Inc.	Indazole-carboxamide compounds
SE532388C2 (sv) *	2008-03-14	2010-01-12	Tetra Laval Holdings & Finance	Förpackningslaminat och -behållare med två separata gasbarriärskikt samt metod för deras framställning
ES2657989T3 (es) *	2013-03-15	2018-03-07	Monsanto Technology Llc	Azoles n-, c-disustituidos para controlar plagas de nematodos
GB201814151D0 (en)	2018-08-31	2018-10-17	Ucl Business Plc	Compounds

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5055476A (en) *	1990-08-13	1991-10-08	Hoechst-Roussel Pharmaceuticals Incorporated	3-(1,2-benzisoxazol-3-yl)-4-pyridinamines and derivatives
JP3294611B2 (ja) *	1991-09-12	2002-06-24	スミスクライン・ビーチャム・パブリック・リミテッド・カンパニー	５−ｈｔ４レセプター・アンタゴニスト
DE69319939T2 (de) *	1992-02-04	1999-02-18	Eisai Co., Ltd., Tokio/Tokyo	Aminobenzoesäure Derivate
JPH07503480A (ja) *	1992-02-06	1995-04-13	スミスクライン・ビーチャム・パブリック・リミテッド・カンパニー	５−ｈｔ４拮抗薬としてのベンゾピラン，ベンゾチオピランおよびベンゾフラン誘導体
JP3235913B2 (ja) *	1993-07-30	2001-12-04	エーザイ株式会社	アミノ安息香酸誘導体
RU2167160C2 (ru) *	1995-11-09	2001-05-20	Санофи-Синтелябо	Производные 5-фенил-3-(пиперидин-4-ил)-1,3,4-оксадиазол-2(3н)-она, способ их получения, фармацевтическая композиция на их основе и лекарственное средство

1997
- 1997-04-18 FR FR9704802A patent/FR2762316B1/fr not_active Expired - Fee Related
1998
- 1998-04-15 TR TR1999/02600T patent/TR199902600T2/xx unknown
- 1998-04-15 PL PL98336315A patent/PL186894B1/pl not_active IP Right Cessation
- 1998-04-15 JP JP54514298A patent/JP2001521542A/ja active Pending
- 1998-04-15 PT PT98920622T patent/PT975631E/pt unknown
- 1998-04-15 CN CN98806195A patent/CN1260794A/zh active Pending
- 1998-04-15 SK SK1426-99A patent/SK283441B6/sk unknown
- 1998-04-15 EP EP98920622A patent/EP0975631B1/de not_active Expired - Lifetime
- 1998-04-15 NZ NZ500396A patent/NZ500396A/en unknown
- 1998-04-15 EE EEP199900487A patent/EE03769B1/xx not_active IP Right Cessation
- 1998-04-15 CA CA002286106A patent/CA2286106A1/en not_active Abandoned
- 1998-04-15 US US09/403,003 patent/US6255319B1/en not_active Expired - Fee Related
- 1998-04-15 RU RU99123933/04A patent/RU2186066C2/ru not_active IP Right Cessation
- 1998-04-15 DK DK98920622T patent/DK0975631T3/da active
- 1998-04-15 BR BR9808926-9A patent/BR9808926A/pt not_active IP Right Cessation
- 1998-04-15 AU AU73415/98A patent/AU742666B2/en not_active Ceased
- 1998-04-15 WO PCT/FR1998/000754 patent/WO1998047898A1/fr not_active Ceased
- 1998-04-15 SI SI9830088T patent/SI0975631T1/xx unknown
- 1998-04-15 IL IL13235298A patent/IL132352A0/xx unknown
- 1998-04-15 KR KR1019997009542A patent/KR20010006452A/ko not_active Ceased
- 1998-04-15 UA UA99105665A patent/UA57071C2/uk unknown
- 1998-04-15 CZ CZ19993641A patent/CZ289154B6/cs not_active IP Right Cessation
- 1998-04-15 AT AT98920622T patent/ATE206424T1/de not_active IP Right Cessation
- 1998-04-15 HU HU0002456A patent/HUP0002456A3/hu unknown
- 1998-04-15 DE DE69801905T patent/DE69801905T2/de not_active Expired - Fee Related
- 1998-04-15 ES ES98920622T patent/ES2165162T3/es not_active Expired - Lifetime
- 1998-04-17 TW TW087105892A patent/TW502005B/zh not_active IP Right Cessation
- 1998-04-17 CO CO98021244A patent/CO4750656A1/es unknown
- 1998-04-17 ZA ZA983257A patent/ZA983257B/xx unknown
- 1998-04-17 AR ARP980101772A patent/AR012458A1/es not_active Application Discontinuation
1999
- 1999-10-15 BG BG103810A patent/BG64053B1/bg unknown
- 1999-10-15 NO NO995040A patent/NO995040L/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
CA2286106A1 (en)	1998-10-29
NO995040D0 (no)	1999-10-15
TR199902600T2 (xx)	2000-03-21
SK142699A3 (en)	2000-05-16
BG103810A (en)	2000-06-30
PL336315A1 (en)	2000-06-19
SK283441B6 (sk)	2003-07-01
RU2186066C2 (ru)	2002-07-27
ES2165162T3 (es)	2002-03-01
DE69801905D1 (de)	2001-11-08
AU742666B2 (en)	2002-01-10
KR20010006452A (ko)	2001-01-26
PL186894B1 (pl)	2004-03-31
JP2001521542A (ja)	2001-11-06
ZA983257B (en)	1998-10-19
DE69801905T2 (de)	2002-07-04
US6255319B1 (en)	2001-07-03
AR012458A1 (es)	2000-10-18
EE9900487A (et)	2000-06-15
SI0975631T1 (en)	2002-06-30
DK0975631T3 (da)	2002-01-28
FR2762316B1 (fr)	1999-12-17
PT975631E (pt)	2002-03-28
CZ364199A3 (cs)	2000-03-15
HUP0002456A3 (en)	2001-03-28
FR2762316A1 (fr)	1998-10-23
BG64053B1 (bg)	2003-11-28
NO995040L (no)	1999-12-16
AU7341598A (en)	1998-11-13
TW502005B (en)	2002-09-11
CZ289154B6 (cs)	2001-11-14
CN1260794A (zh)	2000-07-19
ATE206424T1 (de)	2001-10-15
CO4750656A1 (es)	1999-03-31
IL132352A0 (en)	2001-03-19
EP0975631B1 (de)	2001-10-04
EE03769B1 (et)	2002-06-17
HUP0002456A2 (hu)	2000-12-28
NZ500396A (en)	2001-04-27
BR9808926A (pt)	2000-08-01
EP0975631A1 (de)	2000-02-02
WO1998047898A1 (fr)	1998-10-29

Publication	Publication Date	Title
US5929089A (en)	1999-07-27	5-phenyl-3-(piperidin-4-yl)-1,3,4-oxadiazol-2(3H)-one derivatives for use as 5-Ht4 or H3 receptor ligands
US5330990A (en)	1994-07-19	Substituted urea compounds and their preparation and use
JPH0662607B2 (ja)	1994-08-17	新規三環式化合物
EP1562945A1 (de)	2005-08-17	1,4-dizabicyclo(3,2,2)nonane derivative, verfahren zur ihre herstellung und therapeutical verwendung
UA57071C2 (uk)	2003-06-16	ПОХІДНІ 5-АРИЛ-3-(8-АЗАБІЦИКЛО[3.2.1]ОКТ-3-ІЛ)-1,3,4-ОКСАДІАЗОЛ-2(3Н)-ОНУ ЯК ЛІГАНДИ РЕЦЕПТОРА 5-HT<sub>4</sub>, СПОСІБ ЇХ ОДЕРЖАННЯ, ФАРМАЦЕВТИЧНА КОМПОЗИЦІЯ ТА ЛІКАРСЬКИЙ ЗАСІБ НА ЇХ ОСНОВІ
US20040127491A1 (en)	2004-07-01	Novel diazabicyclic biaryl derivatives
JPH06157518A (ja)	1994-06-03	新規なオキサジアゾール誘導体又はその塩
KR100474454B1 (ko)	2006-03-23	5-ht₄또는h₃수용체리간드로서사용하기위한5-페닐-3-(피페리딘-4-일)-1,3,4-옥사디아졸-2(3h)-온유도체
EP0980370A1 (de)	2000-02-23	5-phenyl-2(3h)-1,3,4-oxadiazolonderivate und ihre verwendung als 5-ht4 liganden
MXPA99009506A (en)	2000-06-01	5-aryl-3-(8-azabicyclo(3.2.2)oct-3-yl)-1,3,4-oxadiazol-2(3h)-one derivatives as 5-ht4 receptor ligands
HK1016165B (en)	2000-09-22	5-phenyl-3-(piperidin-4-yl)-1,3,4-oxadiazol-2(3h)-one derivatives for use as 5-ht4 or h3 receptor ligands